Mecanismos envolvidos no efeito cardiovascular induzido por (-)-mirtenol em ratos hipertensos e normotensos
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFS |
Texto Completo: | http://ri.ufs.br/jspui/handle/riufs/15785 |
Resumo: | Cardiovascular diseases represent a serious public health problem, since they are the main cause of morbidity and mortality in the world. Hypertensive disease is the main cardiovascular disorder and it is estimated that 1.13 billion people have the pathology. The pharmacological treatment of hypertension has some limitations, such as the induction of tolerance and adverse effects, which favor the abandonment of treatment, only one in five hypertensive patients effectively control the disease. (-)-myrtenol, a monoterpene found in various essential oils of plants, induces anxiolytic, antioxidant, cardioprotective activity and can have antihypertensive effect, making it a future alternative for the treatment of hypertension. In this sense, the objective was to determine the mechanisms involved in the cardiovascular effect induced by (-)-myrtenol in hypertensive (SHR) and normotensive (NWR) animals. SHR and NWR animals from 12 - 14 weeks were used, the hemodynamic parameters of blood pressure (BP) and heart rate (HR) were measured after acute and intravenous administration of (-)-myrtenol. The influence of the substance on the autonomic control of cardiovascular function was evaluated with the use of hexamethonium. With the electrocardiogram, the electrical activity of the heart was evaluated after intravenous administration of (-)- mirtenol. The vasorelaxing effect on upper mesenteric artery rings was analyzed in an organ bath system isolated at 37 ° C. Intravenous administration of (-)-myrtenol triggered a dose-dependent hypotensive effect in SHR and NWR animals (p<0.05), with a greater effect in hypertensive animals. In SHR animals, the substance had a biphasic effect (p <0.05) or HR and in NWR animals, reflex tachycardia (p<0.05) occurred. In SHR, in the presence of the ganglionic blocker, hypotension increased at the lowest doses and decreased at the highest dose of (-)-myrtenol (p<0.05). In NWR animals there were no changes in the hypotensive effect in the presence of hexamethonium, only reflex tachycardia was inhibited (p<0.05). In SHR animals, the PRi, QRS and QTc intervals were prolonged (p <0.05) and the amplitude of the R wave reduced (p<0.05), and in NWR animals, only the amplitude of the R wave was reduced (p<0.05). Oral administration of (-) - mirtenol in SHR animals triggered a hypotensive effect after 10 minutes of administration, similarly to nifedipine, this effect decreased with time and bradycardia was maintained for 24 hours. The hypotensive effect of (-) - mirtenol was explained, in part, by the substance's ability to trigger vasorelaxation in the mesenteric artery. In SHR and NWR animals, (-)- myrtenol (10-6 - 3x10-3 mol/L) triggered concentration-dependent vasodilator activity in the pre-contraction induced by phenylephrine with greater effect in SHR animals (p<0.05). The maximum vasorelaxant effect of the substance occurred independently of the vascular endothelium and involved: (I) blocking the influx of calcium into smooth muscle via L-type voltage-sensitive Ca2 + channels, (II) intracellular Ca2 + mobilization and (III) the decrease in the sensitivity of the contractile machinery to the ion. At lower concentrations, the substance stimulated endothelium-dependent vasorelaxation via nitric oxide in SHR (p <0.05). Together, the results showed beneficial cardiovascular effects of (-) - mirtenol in hypertensive and normotensive animals, making it a promising alternative for the development of a future drug. |
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Mendes Neto, José MardenSantos, Sandra Lauton2022-05-27T19:30:33Z2022-05-27T19:30:33Z2020-04-09MENDES NETO, José Marden. Mecanismos envolvidos no efeito cardiovascular induzido por (-)-mirtenol em ratos hipertensos e normotensos. 2020. 142 f. Tese (Doutorado em Ciências Fisiológicas) - Universidade Federal de Sergipe, São Cristóvão, 2020.http://ri.ufs.br/jspui/handle/riufs/15785Cardiovascular diseases represent a serious public health problem, since they are the main cause of morbidity and mortality in the world. Hypertensive disease is the main cardiovascular disorder and it is estimated that 1.13 billion people have the pathology. The pharmacological treatment of hypertension has some limitations, such as the induction of tolerance and adverse effects, which favor the abandonment of treatment, only one in five hypertensive patients effectively control the disease. (-)-myrtenol, a monoterpene found in various essential oils of plants, induces anxiolytic, antioxidant, cardioprotective activity and can have antihypertensive effect, making it a future alternative for the treatment of hypertension. In this sense, the objective was to determine the mechanisms involved in the cardiovascular effect induced by (-)-myrtenol in hypertensive (SHR) and normotensive (NWR) animals. SHR and NWR animals from 12 - 14 weeks were used, the hemodynamic parameters of blood pressure (BP) and heart rate (HR) were measured after acute and intravenous administration of (-)-myrtenol. The influence of the substance on the autonomic control of cardiovascular function was evaluated with the use of hexamethonium. With the electrocardiogram, the electrical activity of the heart was evaluated after intravenous administration of (-)- mirtenol. The vasorelaxing effect on upper mesenteric artery rings was analyzed in an organ bath system isolated at 37 ° C. Intravenous administration of (-)-myrtenol triggered a dose-dependent hypotensive effect in SHR and NWR animals (p<0.05), with a greater effect in hypertensive animals. In SHR animals, the substance had a biphasic effect (p <0.05) or HR and in NWR animals, reflex tachycardia (p<0.05) occurred. In SHR, in the presence of the ganglionic blocker, hypotension increased at the lowest doses and decreased at the highest dose of (-)-myrtenol (p<0.05). In NWR animals there were no changes in the hypotensive effect in the presence of hexamethonium, only reflex tachycardia was inhibited (p<0.05). In SHR animals, the PRi, QRS and QTc intervals were prolonged (p <0.05) and the amplitude of the R wave reduced (p<0.05), and in NWR animals, only the amplitude of the R wave was reduced (p<0.05). Oral administration of (-) - mirtenol in SHR animals triggered a hypotensive effect after 10 minutes of administration, similarly to nifedipine, this effect decreased with time and bradycardia was maintained for 24 hours. The hypotensive effect of (-) - mirtenol was explained, in part, by the substance's ability to trigger vasorelaxation in the mesenteric artery. In SHR and NWR animals, (-)- myrtenol (10-6 - 3x10-3 mol/L) triggered concentration-dependent vasodilator activity in the pre-contraction induced by phenylephrine with greater effect in SHR animals (p<0.05). The maximum vasorelaxant effect of the substance occurred independently of the vascular endothelium and involved: (I) blocking the influx of calcium into smooth muscle via L-type voltage-sensitive Ca2 + channels, (II) intracellular Ca2 + mobilization and (III) the decrease in the sensitivity of the contractile machinery to the ion. At lower concentrations, the substance stimulated endothelium-dependent vasorelaxation via nitric oxide in SHR (p <0.05). Together, the results showed beneficial cardiovascular effects of (-) - mirtenol in hypertensive and normotensive animals, making it a promising alternative for the development of a future drug.As doenças cardiovasculares representam um grave problema de saúde pública, uma vez que são a principal causa de morbimortalidade no mundo. A doença hipertensiva é o principal distúrbio cardiovascular e estima-se que 1,13 bilhões de pessoas possuam a patologia. O tratamento farmacológico da hipertensão apresenta algumas limitações como, a indução de tolerância e efeitos adversos, que favorecem o abandono do tratamento, apenas um a cada cinco hipertensos controlam efetivamente a doença. O (- )- mirtenol, um monoterpeno encontrado em vários óleos essenciais de plantas, desencadeia atividade ansiolítica, antioxidante, cardioprotetora e pode apresentar efeito anti-hipertensivo, tornando-se uma alternativa futura para o tratamento da hipertensão. Neste sentido, objetivou-se determinar os mecanismos envolvidos no efeito cardiovascular induzido por (-)-mirtenol em animais hipertensos (SHR) e normotensos (RWN). Utilizou-se animais SHR e RWN de 12 – 14 semanas, os parâmetros hemodinâmicos de pressão arterial (PA) e frequência cardíaca (FC) foram aferidos após a administração oral e intravenosa do (-)-mirtenol, de forma aguda. A influência da substância no controle autonômico da função cardiovascular foi avaliada com a utilização de hexametônio. Com o eletrocardiograma, avaliou-se a atividade elétrica do coração após a administração intravenosa do (-)-mirtenol. O efeito vasorrelaxante em anéis de artéria mesentérica superior foi analisado em sistema de banho para órgão isolado à 37°C. A administração intravenosa do (-)-mirtenol desencadeou efeito hipotensor dependente de dose em animais SHR e RWN (p<0,05), com maior efeito em animais hipertensos. Na FC, em animais SHR, a substância apresentou um efeito bifásico (p<0,05) e nos animais RWN, ocorreu taquicardia reflexa (p<0,05). Em SHR, o bloqueador ganglionar induziu maior queda na PA nas menores doses e inibiu a hipotensão na mais alta dose do (-)- mirtenol (p<0,05). Em animais RWN não houve alterações no efeito hipotensor na presença do hexametônio, apenas a taquicardia reflexa foi inibida (p<0,05). Em animais SHR, os intervalos PRi, QRS e QTc foram prolongados (p<0,05) e a amplitude da onda R foi reduzida (p<0,05), e nos animais RWN, apenas a amplitude da onda R foi reduzida (p<0,05). A administração oral do (-)-mirtenol em animais SHR desencadeou efeito hipotensor após 10 minutos da administração, semelhantemente, ao nifedipino, tal efeito diminuiu com o tempo e a bradicardia se manteve durante as 24 horas acompanhadas. O efeito hipotensor do (-)-mirtenol foi explicado, em parte, pela capacidade da substância em desencadear vasorrelaxamento em artéria mesentérica. Em animais SHR e RWN, o (- )-mirtenol (10 - 6 – 3x10-3 mol/L) desencadeou atividade vasodilatadora dependente de concentração na pré-contração induzida por fenilefrina com maior efeito em animais SHR (p<0,05). O efeito vasorrelaxante máximo da substância, ocorreu de modo independente do endotélio vascular e envolveu: (I) o bloqueio do influxo de cálcio na musculatura lisa via canais para Ca2+ sensíveis a voltagem do tipo L, (II) a mobilização de Ca2+ intracelular e (III) a diminuição na sensibilidade da maquinaria contrátil ao íon. Nas menores concentrações a substância estimulou o vasorrelaxamento dependente do endotélio via óxido nítrico em SHR (p<0,05). Em conjunto, os resultados evidenciaram efeitos cardiovasculares benéficos do (-)-mirtenol em animais hipertensos e normotensos, tornando-se uma promissora alternativa para o desenvolvimento de um fármaco futuro.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESFundação de Apoio a Pesquisa e à Inovação Tecnológica do Estado de Sergipe - FAPITEC/SESão CristóvãoporHipertensãoBradicardiaEletrocardiografiaVasos sanguíneosVasodilataçãoMonoterpenosHypotensionBradycardiaEletrocardiographyVasodilatationMonoterpenesCIENCIAS BIOLOGICAS::FISIOLOGIAMecanismos envolvidos no efeito cardiovascular induzido por (-)-mirtenol em ratos hipertensos e normotensosinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisPós-Graduação em Ciências FisiológicasUniversidade Federal de Sergipereponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81475https://ri.ufs.br/jspui/bitstream/riufs/15785/1/license.txt098cbbf65c2c15e1fb2e49c5d306a44cMD51ORIGINALJOSE_MARDEN_MENDES_NETO.pdfJOSE_MARDEN_MENDES_NETO.pdfapplication/pdf2436191https://ri.ufs.br/jspui/bitstream/riufs/15785/2/JOSE_MARDEN_MENDES_NETO.pdf1736773f485a1ecabf981f53f2f4ae28MD52TEXTJOSE_MARDEN_MENDES_NETO.pdf.txtJOSE_MARDEN_MENDES_NETO.pdf.txtExtracted texttext/plain268380https://ri.ufs.br/jspui/bitstream/riufs/15785/3/JOSE_MARDEN_MENDES_NETO.pdf.txtb70af4d12f68d85c1f2f39b4b451c089MD53THUMBNAILJOSE_MARDEN_MENDES_NETO.pdf.jpgJOSE_MARDEN_MENDES_NETO.pdf.jpgGenerated Thumbnailimage/jpeg1367https://ri.ufs.br/jspui/bitstream/riufs/15785/4/JOSE_MARDEN_MENDES_NETO.pdf.jpg9266feb8b5b497867ec92458a96f1478MD54riufs/157852022-05-27 16:31:31.382oai:ufs.br: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Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2022-05-27T19:31:31Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false |
dc.title.pt_BR.fl_str_mv |
Mecanismos envolvidos no efeito cardiovascular induzido por (-)-mirtenol em ratos hipertensos e normotensos |
title |
Mecanismos envolvidos no efeito cardiovascular induzido por (-)-mirtenol em ratos hipertensos e normotensos |
spellingShingle |
Mecanismos envolvidos no efeito cardiovascular induzido por (-)-mirtenol em ratos hipertensos e normotensos Mendes Neto, José Marden Hipertensão Bradicardia Eletrocardiografia Vasos sanguíneos Vasodilatação Monoterpenos Hypotension Bradycardia Eletrocardiography Vasodilatation Monoterpenes CIENCIAS BIOLOGICAS::FISIOLOGIA |
title_short |
Mecanismos envolvidos no efeito cardiovascular induzido por (-)-mirtenol em ratos hipertensos e normotensos |
title_full |
Mecanismos envolvidos no efeito cardiovascular induzido por (-)-mirtenol em ratos hipertensos e normotensos |
title_fullStr |
Mecanismos envolvidos no efeito cardiovascular induzido por (-)-mirtenol em ratos hipertensos e normotensos |
title_full_unstemmed |
Mecanismos envolvidos no efeito cardiovascular induzido por (-)-mirtenol em ratos hipertensos e normotensos |
title_sort |
Mecanismos envolvidos no efeito cardiovascular induzido por (-)-mirtenol em ratos hipertensos e normotensos |
author |
Mendes Neto, José Marden |
author_facet |
Mendes Neto, José Marden |
author_role |
author |
dc.contributor.author.fl_str_mv |
Mendes Neto, José Marden |
dc.contributor.advisor1.fl_str_mv |
Santos, Sandra Lauton |
contributor_str_mv |
Santos, Sandra Lauton |
dc.subject.por.fl_str_mv |
Hipertensão Bradicardia Eletrocardiografia Vasos sanguíneos Vasodilatação Monoterpenos |
topic |
Hipertensão Bradicardia Eletrocardiografia Vasos sanguíneos Vasodilatação Monoterpenos Hypotension Bradycardia Eletrocardiography Vasodilatation Monoterpenes CIENCIAS BIOLOGICAS::FISIOLOGIA |
dc.subject.eng.fl_str_mv |
Hypotension Bradycardia Eletrocardiography Vasodilatation Monoterpenes |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::FISIOLOGIA |
description |
Cardiovascular diseases represent a serious public health problem, since they are the main cause of morbidity and mortality in the world. Hypertensive disease is the main cardiovascular disorder and it is estimated that 1.13 billion people have the pathology. The pharmacological treatment of hypertension has some limitations, such as the induction of tolerance and adverse effects, which favor the abandonment of treatment, only one in five hypertensive patients effectively control the disease. (-)-myrtenol, a monoterpene found in various essential oils of plants, induces anxiolytic, antioxidant, cardioprotective activity and can have antihypertensive effect, making it a future alternative for the treatment of hypertension. In this sense, the objective was to determine the mechanisms involved in the cardiovascular effect induced by (-)-myrtenol in hypertensive (SHR) and normotensive (NWR) animals. SHR and NWR animals from 12 - 14 weeks were used, the hemodynamic parameters of blood pressure (BP) and heart rate (HR) were measured after acute and intravenous administration of (-)-myrtenol. The influence of the substance on the autonomic control of cardiovascular function was evaluated with the use of hexamethonium. With the electrocardiogram, the electrical activity of the heart was evaluated after intravenous administration of (-)- mirtenol. The vasorelaxing effect on upper mesenteric artery rings was analyzed in an organ bath system isolated at 37 ° C. Intravenous administration of (-)-myrtenol triggered a dose-dependent hypotensive effect in SHR and NWR animals (p<0.05), with a greater effect in hypertensive animals. In SHR animals, the substance had a biphasic effect (p <0.05) or HR and in NWR animals, reflex tachycardia (p<0.05) occurred. In SHR, in the presence of the ganglionic blocker, hypotension increased at the lowest doses and decreased at the highest dose of (-)-myrtenol (p<0.05). In NWR animals there were no changes in the hypotensive effect in the presence of hexamethonium, only reflex tachycardia was inhibited (p<0.05). In SHR animals, the PRi, QRS and QTc intervals were prolonged (p <0.05) and the amplitude of the R wave reduced (p<0.05), and in NWR animals, only the amplitude of the R wave was reduced (p<0.05). Oral administration of (-) - mirtenol in SHR animals triggered a hypotensive effect after 10 minutes of administration, similarly to nifedipine, this effect decreased with time and bradycardia was maintained for 24 hours. The hypotensive effect of (-) - mirtenol was explained, in part, by the substance's ability to trigger vasorelaxation in the mesenteric artery. In SHR and NWR animals, (-)- myrtenol (10-6 - 3x10-3 mol/L) triggered concentration-dependent vasodilator activity in the pre-contraction induced by phenylephrine with greater effect in SHR animals (p<0.05). The maximum vasorelaxant effect of the substance occurred independently of the vascular endothelium and involved: (I) blocking the influx of calcium into smooth muscle via L-type voltage-sensitive Ca2 + channels, (II) intracellular Ca2 + mobilization and (III) the decrease in the sensitivity of the contractile machinery to the ion. At lower concentrations, the substance stimulated endothelium-dependent vasorelaxation via nitric oxide in SHR (p <0.05). Together, the results showed beneficial cardiovascular effects of (-) - mirtenol in hypertensive and normotensive animals, making it a promising alternative for the development of a future drug. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020-04-09 |
dc.date.accessioned.fl_str_mv |
2022-05-27T19:30:33Z |
dc.date.available.fl_str_mv |
2022-05-27T19:30:33Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
MENDES NETO, José Marden. Mecanismos envolvidos no efeito cardiovascular induzido por (-)-mirtenol em ratos hipertensos e normotensos. 2020. 142 f. Tese (Doutorado em Ciências Fisiológicas) - Universidade Federal de Sergipe, São Cristóvão, 2020. |
dc.identifier.uri.fl_str_mv |
http://ri.ufs.br/jspui/handle/riufs/15785 |
identifier_str_mv |
MENDES NETO, José Marden. Mecanismos envolvidos no efeito cardiovascular induzido por (-)-mirtenol em ratos hipertensos e normotensos. 2020. 142 f. Tese (Doutorado em Ciências Fisiológicas) - Universidade Federal de Sergipe, São Cristóvão, 2020. |
url |
http://ri.ufs.br/jspui/handle/riufs/15785 |
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por |
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openAccess |
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Pós-Graduação em Ciências Fisiológicas |
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Universidade Federal de Sergipe |
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